Nanomaterials for the integration of soft into hard tissue

Abstract

Nanocomposite materials are provided for attaching soft tissue to hard tissue of a mammalian subject. The materials include a biodegradable polymer network suffused with mineral nanoparticles. The nanocomposite materials have a surface structure that promotes the infiltration, adhesion and proliferation of cells such as osteoblasts and fibroblasts, and are useful to reconstruct enthesis tissue, such as a tendon bone insertion. Devices containing the nanocomposites and methods for implantation of the devices at a tendon-bone interface or ligament-bone interface are provided for reconstructive surgery.

1 . A composite material comprising a biodegradable polymer matrix, a plurality of MgO nanoparticles embedded in the matrix, and a plurality of hydroxyapatite nanoparticles embedded in the matrix. 
     
     
         2 - 6 . (canceled) 
     
     
         7 . The material of  claim 1 , wherein the hydroxyapatite nanoparticles are present at about 10 wt % to about 60 wt %. 
     
     
         8 . The material of  claim 7  comprising about 10 wt % MgO nanoparticles. 
     
     
         9 . The material of  claim 8  comprising about 10 wt % hydroxyapatite nanoparticles. 
     
     
         10 . The material of  claim 1 , further comprising a plurality of adsorbed cells. 
     
     
         11 . (canceled) 
     
     
         12 . The material of  claim 1 , wherein the MgO nanoparticles are present in a gradient of concentration through the material. 
     
     
         13 . The material of  claim 1 , wherein the hydroxyapatite nanoparticles are present in a gradient of concentration through the material. 
     
     
         14 . The material of  claim 1 , wherein a surface of the material promotes cell adhesion. 
     
     
         15 . (canceled) 
     
     
         16 . The material of  claim 1 , wherein a surface of the material promotes cell proliferation. 
     
     
         17 . (canceled) 
     
     
         18 . The material of  claim 1 , further comprising one or more growth factors. 
     
     
         19 . The material of  claim 18 , wherein the material comprises dexamethasone. 
     
     
         20 . An enthesis regeneration device comprising the composite material of  claim 1  formed into a ring-shaped structure and having an inner surface and an outer surface, the inner surface configured to surround a tendon, ligament, or cell scaffold and the outer surface configured to fit within a bone cavity. 
     
     
         21 . The device of  claim 20  having an inside ring diameter and an outside ring diameter, wherein the inside diameter is selected to provide contact of the device with said tendon, ligament, or cell scaffold and wherein the outside diameter is selected to provide contact with an inner surface of said bone cavity. 
     
     
         22 . The device of  claim 21 , wherein the ligament is an anterior cruciate ligament. 
     
     
         23 . The device of  claim 21 , wherein the inside diameter is about 10 mm. 
     
     
         24 . The device of  claim 21 , wherein the outside diameter is about 14 mm. 
     
     
         25 . The device of  claim 21 , wherein the ring-shaped structure has a wall thickness of about 2 mm. 
     
     
         26 . The device of  claim 21 , wherein MgO nanoparticles in the material form a gradient from a lower concentration at said inner surface to a higher concentration at said outer surface. 
     
     
         27 . (canceled) 
     
     
         28 . The device of  claim 1 , wherein the hydroxyapatite nanoparticles form a gradient from a lower concentration at said inner surface to a higher concentration at said outer surface. 
     
     
         29 . The device of  claim 28 , wherein MgO nanoparticles in the material form a gradient from a lower concentration at said inner surface to a higher concentration at said outer surface. 
     
     
         30 . A method of fabricating the composite material of  claim 1 , the method comprising the steps of:
 (a) providing a solution of poly(L-lactic acid) in a solvent;   (b) suspending MgO nanoparticles and hydroxyapatite nanoparticles in the solution to form a suspension;   (c) placing the suspension in a mold; and   (d) removing the solvent to form the composite material.   
     
     
         31 . The method of  claim 30 , wherein the solvent is removed by heating. 
     
     
         32 . The method of  claim 30 , wherein the composite material is produced in sheet form. 
     
     
         33 . (canceled) 
     
     
         34 . A method of attaching a ligament or tendon to a bone, the method comprising the steps of
 (a) attaching the enthesis regeneration device of  claim 21  to a detached end of a ligament or tendon, whereby the device surrounds the detached end;   (b) anchoring the detached end of the ligament or tendon within a hole or tunnel in a bone of an animal; and   (c) allowing the device to form a new enthesis between the bone and the ligament or tendon.   
     
     
         35 . A method of attaching a soft tissue to a hard tissue, the method comprising the steps of:
 (a) attaching a device comprising the composite material of  claim 1  to a soft tissue;   (b) anchoring the device and attached soft tissue to a hard tissue; and   (c) allowing cell attachment and proliferation within the device to attach the soft tissue to the hard tissue.   
     
     
         36 . A kit comprising the enthesis regeneration device of  claim 21  and a container for the device. 
     
     
         37 . The kit of  claim 36  further comprising one or more tools for attaching the device to a tissue.